Salivary gland cancers comprise a heterogeneous group
of neoplasms whose biological and clinical
characteristics differ considerably from those of
mucosal squamous cell carcinomas of the head and neck.
One of the most common subtypes, adenoid cystic
carcinoma (ACC), is notable for its myoepithelial
differentiation, proclivity for hematogenous spread,
and slow but progressive clinical course. The
molecular alterations that underlie its development
and progression are poorly characterized. Here we used
oligonucleotide microarray analysis to survey the
expression of 8920 different human genes in 15 ACCs,
one ACC cell line, and five normal major salivary
glands. We observed expression of genes indicative of
myoepithelial differentiation, as expected, including
those whose protein products are components of
basement membranes and extracellular matrix. Other
genes that were highly ranked for their expression in
ACC were those encoding the transcription factors SOX4
and AP-2 , the latter of which also was overexpressed
in ACC relative to 175 other carcinomas from 10
anatomical sites that we had previously profiled.
Additional genes, which were highly expressed in ACC
compared to the other carcinomas, included casein
kinase 1, epsilon and frizzled-7, both members of the
Wnt/ß-catenin signaling pathway. Our study documents
for the first time the diverse spectrum of genes
overexpressed in ACC and highlights gene products and
pathways that in the future might be exploited as
therapeutic targets for this cancer, which up until
now, has shown limited response to chemotherapeutic
approaches.